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ANH-Intl Covid-19 information tracker - Week 22
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Science |
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Epidemiology |
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Authors: Sheervalilou R et al Publication date: 26 May 2020 Journal: Journal of Cellular Physiology DOI: 10.1002/jcp.29735 Months after the outbreak of a new flu‐like disease in China, the entire world is now in a state of caution. The subsequent less‐anticipated propagation of the novel coronavirus disease, formally known as COVID‐19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS‐CoV‐2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID‐19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed. Authors: Neeraj Sood PhD, Paul Simon MD and Peggy Ebner Publication date: 18 May 2020 Journal: JAMA DOI: 10.1001/jama.2020.8279 Inadequate knowledge about the extent of the coronavirus disease 2019 (COVID-19) epidemic challenges public health response and planning. Most reports of confirmed cases rely on polymerase chain reaction–based testing of symptomatic patients.1 These estimates of confirmed cases miss individuals who have recovered from infection, with mild or no symptoms, and individuals with symptoms who have not been tested due to limited availability of tests. We conducted serologic tests in a community sample to estimate cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as serologic tests identify both active and past infections. |
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Pathogenesis |
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Authors: Aristo Vojdani and Datis Kharrazian Publication date: 24 May 2020 Journal: Clinical Immunology DOI: 10.1016/j.clim.2020.108480 Since the outbreak of COVID-19 caused by SARS-CoV-2, we tested 5 different blood specimens that were confirmed positive for SARS-CoV-2 IgG and IgM antibodies [1]. The measurements were for anti-nuclear antibody (ANA), anti-extractable nuclear antigen (ENA), anti-double-stranded DNA (dsDNA), actin antibody, mitochondrial antibody, rheumatoid factor (RF), and C1q immune complexes. We were surprised to find out that 3 of the 5 specimens had significant elevations in ANA, ENA, actin and mitochondrial antibodies, but not against dsDNA or RF. This prompted us to investigate patterns of cross-reactivity between SARS-CoV-2 and autoimmune target proteins. Vaccine-induced autoimmunity from autoimmune cross-reactivity is associated with narcolepsy, Guillain-Barré syndrome, multiple sclerosis, demyelinating neuropathies, systemic lupus erythematosus, and postural orthostatic tachycardia syndrome in susceptible subgroups as reported by Segal and Shoenfeld [2]. Due to the significant red flags for the potential cross-reactive interactions with the current COVID-19 pandemic, we studied the relationships between spike and nuclear proteins of SARS-CoV-2 and autoimmune target proteins. Coronaviruses pathogenesis, comorbidities and multi-organ damage – A review Authors: Renu K et al Publication date: 22 May 2020 Journal: Life Sciences DOI: 10.1016/j.lfs.2020.117839 Human coronaviruses, especially COVID-19, is an emerging pandemic infectious disease with high morbidity and mortality. Coronaviruses are associated with comorbidities, along with the symptoms of it. SARS-CoV-2 is one of the highly pathogenic coronaviruses that causes a high death rate compared to the SARS-CoV and MERS. In this review, we focused on the mechanism of coronavirus with comorbidities and impairment in multi-organ function. The main dysfunction upon coronavirus infection is damage to alveolar and acute respiratory failure. It is associated with the other organ damage such as cardiovascular risk via an increased level of hypertension through ACE2, gastrointestinal dysfunction, chronic kidney disease, diabetes mellitus, liver dysfunction, lung injury, CNS risk, ocular risks such as chemosis, conjunctivitis, and conjunctival hyperemia, cancer risk, venous thromboembolism, tuberculosis, aging, and cardiovascular dysfunction and reproductive risk. Along with this, we have discussed the immunopathology and coronaviruses at a molecular level and therapeutic approaches for the coronavirus infection. The comorbidities and multi-organ failure of COVID-19 have been explained at a molecular level along with the base of the SARS-CoV and MERS-CoV. This review would help us to understand the comorbidities associated with the coronaviruses with multi-organ damage. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19 Authors: Blanco-Meol D et al Publication date: 15 May 2020 Journal: Cell DOI: 10.1016/j.cell.2020.04.026 Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19. |
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Covid-19 and pregnancy |
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Placental Pathology in COVID-19 Authors: Shanes ED et al Publication date: 22 May 2020 Journal: American Journal of Clinical Pathology DOI: 10.1093/ajcp/aqaa089 Objectives: To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. Methods: Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. Results: Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. Conclusions: Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology. COVID-19 and pregnancy – where are we now? A review Authors: Rajewsak A et al Publication date: 11 May 2020 Journal: Journal of Perinatal Medicine DOI: 10.1515/jpm-2020-0132 The new acute respiratory disease severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious. It has caused many deaths, despite a relatively low general case fatality rate (CFR). The most common early manifestations of infection are fever, cough, fatigue and myalgia. The diagnosis is based on the exposure history, clinical manifestation, laboratory test results, chest computed tomography (CT) findings and a positive reverse transcription-polymerase chain reaction (RT-PCR) result for coronavirus disease 2019 (COVID-19). The effect of SARS-CoV-2 on pregnancy is not already clear. There is no evidence that pregnant women are more susceptible than the general population. In the third trimester, COVID-19 can cause premature rupture of membranes, premature labour and fetal distress. There are no data on complications of SARS-CoV-2 infection before the third trimester. COVID-19 infection is an indication for delivery if necessary to improve maternal oxygenation. Decision on delivery mode should be individualised. Vertical transmission of coronavirus from the pregnant woman to the fetus has not been proven. As the virus is absent in breast milk, the experts encourage breastfeeding for neonatal acquisition of protective antibodies. |
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Covid-19 patients |
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UK report on 9026 patients critically ill with COVID-19 Institution: Intensive Care National Audit & Research Centre (ICNARC) Publication date: 22 May 2020 Read more... Authors: Docherty AB et al Publication date: 22 May 2020 Journal: The BMJ DOI: 10.1136/bmj.m1985 Objective: To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital. Results: The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. Conclusions: ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series Authors: Bhatraju PK et al Publication date: 21 May 2020 Journal: New England Journal of Medicine DOI: 10.1056/NEJMoa2004500 Background: Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. Methods: We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. Results: We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. Conclusions: During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. Olfactory Dysfunction in COVID-19 Authors: Katherine Lisa Whitcroft and Thomas Hummel MD Publication date: 20 May 2020 Journal: JAMA DOI: 10.1001/jama.2020.8391 As of May 1, 2020, more than 3 000 000 people worldwide have been infected with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CDC has highlighted key symptoms that may suggest coronavirus disease 2019 (COVID-19), including cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, and new loss of smell or taste. The inclusion of loss of smell or taste among these symptoms follows the emergence of evidence that suggests that COVID-19 frequently impairs the sense of smell. For example, in a study from Iran, 59 of 60 patients hospitalized with COVID-19 were found to have an impaired sense of smell according to psychophysical olfactory testing.2 Olfactory dysfunction (OD), defined as the reduced or distorted ability to smell during sniffing (orthonasal olfaction) or eating (retronasal olfaction), is often reported in mild or even asymptomatic cases; in a study from Italy, 64% of 202 mildly symptomatic patients reported impaired olfaction.3 The possibility that OD could act as a marker for disease, particularly among individuals who are otherwise minimally symptomatic or asymptomatic, prompted organizations, such as the American Academy of Otolaryngology–Head and Neck Surgery4 and ENT UK,5 to recommend inclusion of sudden-onset loss of smell and/or taste as part of the diagnostic criteria for COVID-19 disease, as has now been done by the CDC. These organizations suggest that new-onset OD is sufficient to justify self-isolation and the use of personal protective equipment (PPE) by medical staff evaluating patients with this clinical problem. |
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Co-morbidities |
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Authors: Vageesh Jain & Jin-Min Yan Publication date: 25 May 2020 Journal: International Journal of Public Health DOI: 10.1007/s00038-020-01390-7 Objectives: COVID-19 has a varied clinical presentation. Elderly patients with comorbidities are more vulnerable to severe disease. This study identifies specific symptoms and comorbidities predicting severe COVID-19 and intensive care unit (ICU) admission. Methods: A literature search identified studies indexed in MEDLINE, EMBASE and Global Health before 5th March 2020. Two reviewers independently screened the literature and extracted data. Quality appraisal was performed using STROBE criteria. Random effects meta-analysis identified symptoms and comorbidities associated with severe COVID-19 or ICU admission. Results: Seven studies (including 1813 COVID-19 patients) were included. ICU patients were older (62.4 years) than non-ICU (46 years), with a greater proportion of males. Dyspnoea was the only symptom predictive for severe disease (pOR 3.70, 95% CI 1.83–7.46) and ICU admission (pOR 6.55, 95% CI 4.28–10.0). COPD was the strongest predictive comorbidity for severe disease (pOR 6.42, 95% CI 2.44–16.9) and ICU admission (pOR 17.8, 95% CI 6.56–48.2), followed by cardiovascular disease and hypertension. Conclusions: Dyspnoea was the only symptom predictive for severe COVID-19 and ICU admission. Patients with COPD, cardiovascular disease and hypertension were at higher risk of severe illness and ICU admission. Authors: Klang E et al Publication date: 23 May 2020 Journal: Obesity DOI: 10.1002/oby.22913 Objective: COVID‐19 continues to spread and younger patients are also being critically affected. This study analyzed obesity as an independent risk factor for mortality in hospitalized patients younger than fifty. Methods: We retrospectively nalysed data of COVID‐19 patients hospitalized to a large academic hospital system in New York City between March 1st and May 17th, 2020. Data included demographics, comorbidities, BMI and smoking status. Obesity groups included: BMI 30–40 kg/m2 and BMI ≥ 40 kg/m2. Multivariable logistic regression models identified variables independently associated with mortality in patients younger and older than 50. Results: Overall, 3,406 patients were included. 572 (17.0%) of the patients were younger than 50. In the younger age group, 60 (10.5%) patients died. In the older age group, 1,076 (38.0%) patients died. For the younger population, BMI above 40 kg/m2 was independently associated with mortality (aOR 5.1, 95% CI 2.3–11.1). For the older population, BMI above 40 kg/m2 was also independently associated with mortality to a lesser extent (aOR 1.6, 95% CI 1.2 – 2.3). Conclusion: Our study demonstrates that hospitalized patients younger than 50 with morbid obesity are more likely to die from COVID‐19. This is particularly relevant in the western world where obesity rates are high. Prevalence of obesity among adult inpatients with COVID-19 in France Authors: Caussy C et al Publication date: 18 May 2020 Journal: The Lancet Diabetes & Endocriniology DOI: 10.1016/S2213-8587(20)30160-1 Most people who develop COVID-19 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection present with paucisymptomatic and non-severe disease.1 However, approximately 20% of patients develop severe COVID-19 requiring hospitalisation, including 5% who are admitted to the intensive care unit (ICU).2 The ongoing COVID-19 outbreak has led to an unprecedented health crisis. Hence, it is crucial to identify individuals who are susceptible to developing severe COVID-19 and could require hospitalisation, especially in the ICU. Evidence is emerging that obesity-related conditions seem to worsen the effect of the virus. Studies from Chinese cohorts of patients with COVID-19 have identified several risk factors of severe COVID-19 including age, cardiomyopathy, and obesity-related complications such as type 2 diabetes and hypertension. However, to our knowledge, only few studies so far have included information regarding the BMI of patients with COVID-19, which suggest a high prevalence of obesity in patients with severe COVID-19.4, 5, 6, 7 Data from New York City suggest that obesity, as defined by BMI of at least 30 kg/m2, might be a risk factor for ICU admission among patients with COVID-19, especially among those younger than 60 years.8 Additionally, preliminary analyses from Lille University Hospital have reported differences in BMI distribution in ICU patients with COVID-19 compared with ICU patients without COVID-19. Two important controversial risk factors in SARS-CoV-2 infection: Obesity and smoking Authors: Ayse Basak Engin, Evren Doruk Engin and Atilla Engin Publication date: 15 May 2020 Journal: Environmental Toxicology and Pharmacology DOI: 10.1016/j.etap.2020.103411 The effects of obesity and smoking in the coronavirus disease 2019 (COVID-19) pandemic remain controversial. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), is the human cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. ACE2 expression increases on lung alveolar epithelial cells and adipose tissue due to obesity, smoking and air pollution. A significant relationship exists between air pollution and SARS-CoV-2 infection, as more severe COVID-19 symptoms occur in smokers; comorbid conditions due to obesity or excess ectopic fat accumulation as underlying risk factors for severe COVID-19 strongly encourage the virus/ACE2 receptor-ligand interaction concept. Indeed, obesity, air pollution and smoking associated risk factors share underlying pathophysiologies that are related to the Renin-Angiotensin-System in SARS-CoV-2 infection. The aim of this review is to emphasize the mechanism of receptor-ligand interaction and its impact on the enhanced risk of death due to SARS-CoV-2 infection. |
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Coronavirus in children |
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Children appear half as likely to catch COVID-19 as adults Publication date: 22 May 2020 Source: UCL News Children and young people appear to be more than 50% less likely to catch SARS-CoV-2, the virus that causes COVID-19, than adults but evidence remains weak on how likely they are to transmit the virus, finds a UCL-led review of test and tracing and population screening studies. |
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Therapeutics |
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Authors: Mehra MR Prof et al Publication date: 22 May 2020 Journal: The Lancet DOI: 10.1016/S0140-6736(20)31180-6 We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19. Vitamin D and SARS-CoV-2 virus/COVID-19 disease Authors: Lanham-New SA et al Publication date: 30 April 2020 DOI: 10.1136/bmjnph-2020-000089 The spread of novel SARS-CoV-2 virus, and the disease COVID-19 that is caused by SARS-CoV-2, continues apace. Saving lives and slowing the worldwide pandemic remain of utmost importance to everyone: the public, healthcare professionals, scientists, industry and governments. It is absolutely essential that advice given to the public is evidence-based, accurate and timely; anything less would mislead and has the potential to cause harm. Popular information channels, such as social media platforms, have been rife with misinformation that has been perpetuated by fear and uncertainty. This has been the case particularly for diet and lifestyle advice. There are recommendations for the prevention of the spread of COVID-19 from the WHO,1 the UK,2 Irish3 and USA4 governments and the European Commission,5 as well as public health and healthcare agencies, including key direction on self-isolation.6 This short original report aims to provide a balanced scientific view on vitamin D and SARS-CoV-2 virus/COVID-19 disease. It provides a succinct summary of the current scientific evidence of associations between vitamin D, influenza, upper respiratory tract infections (URTIs) and immune health. Importantly, the paper concludes with lifestyle strategies for avoiding vitamin D deficiency and ensuring a healthy balanced diet at any time, including during the current pandemic. The overarching messages are as follows: (1) Vitamin D is essential for good health. (2) Many people, particularly those living in northern latitudes (such as the UK, Ireland, Northern Europe, Canada and the northern parts of the USA, northern India and China), have poor vitamin D status, especially in winter or if confined indoors. (3) Low vitamin D status may be exacerbated during this COVID-19 crisis (eg, due to indoor living and hence reduced sun exposure), and anyone who is self-isolating with limited access to sunlight is advised to take a vitamin D supplement according to their government’s recommendations for the general population (ie, 400 IU/day for the UK7 and 600 IU/day for the USA (800 IU for >70 years))8 and the European Union (EU).9 (4) There is no strong scientific evidence to show that very high intakes (ie, mega supplements) of vitamin D will be beneficial in preventing or treating COVID-19. (5) There are evidenced health risks with excessive vitamin D intakes especially for those with other health issues such as a reduced kidney function. |
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Antibodies |
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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals Authors: Robbiani DF et al Publication date: 22 May 2020 Journal: bioRxiv preprint DOI: 10.1101/2020.05.13.092619 During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective. |
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Vaccines |
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Authors: Zhu FC Prof et al Publication date: 22 May 2020 Journal: The Lancet DOI: 10.1016/S0140-6736(20)31208-3 Background: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Methods: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Findings: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. Interpretation: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. Planning for a COVID-19 Vaccination Program Authors: Sarah Schaffer, Natalie J Pudalov, Linda Y Fu Publication date: 18 May 2020 Journal: JAMA DOI: 10.1001/jama.2020.8711 The long-term solution to the coronavirus disease 2019 (COVID-19) pandemic, hopefully, will be a globally implemented, safe vaccination program that has broad clinical and socioeconomic benefits. Dozens of vaccines are in development, with 8 currently in phase 1 trials. Some scenarios predict the earliest, widespread availability of a COVID-19 vaccine to be in 2021.1 As launches of prior mass vaccination programs have demonstrated, careful planning to ensure readiness of both the general public and the health community for a COVID-19 vaccine should begin now. To substantially reduce morbidity and mortality from COVID-19, an efficacious and safe vaccine must be delivered swiftly and broadly to the public as soon as it is available. However, the mere availability of a vaccine is insufficient to guarantee broad immunological protection; the vaccine must also be acceptable to both the health community and general public. Vaccine hesitancy is a major barrier to vaccine uptake and the achievement of herd immunity, which is required to protect the most vulnerable populations. Depending on varying biological, environmental, and sociobehavioral factors, the threshold for COVID-19 herd immunity may be between 55% and 82% of the population. The online competition between pro- and anti-vaccination views Authors: Johnson NF et al Publication date: 13 May 2020 Journal: Nature DOI: 10.1038/s41586-020-2281-1 Distrust in scientific expertise1–14 is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks2–4, as happened for measles in 20195,6. Homemade remedies7,8 and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice9–11. There is a lack of understanding about how this distrust evolves at the system level13,14. Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change11, and highlight the key role of network cluster dynamics in multi-species ecologies. |
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Pathology |
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Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 Authors: Ackermann M etal Publication date: 21 May 2020 Journal: New England Journal of Medicine DOI: 10.1056/NEJMoa2015432 Background: Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. Methods: We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro–computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression. Results: In patients who died from Covid-19–associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001). Conclusions: In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19 Authors: Wichmann D MD et al Publication date: 6 May 2020 Journal: Annals of Internal Medicine DOI: 10.7326/M20-2003 Background: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. Objective: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. Setting: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. Patients: The first 12 consecutive COVID-19–positive deaths. Measurements: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. Conclusion: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy Authors: Carasana L et al Publication date: 22 April 2020 Journal: medRxiv preprint DOI: 10.1101/2020.04.19.20054262 Importance. The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness. Objective. To determine the histological patterns in lung tissue of patients with severe COVID-19. Design and participants. Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed. Results. The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstitium. Electron microscopy revealed viral particles within cytoplasmic vacuoles of pneumocytes. Conclusions and relevance. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy. |
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Immune system |
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SARS‐CoV‐2 infection‐induced immune responses: friends or foes? Authors: Li K et al Publication date: 23 May 2020 Journal: Scandinavian Journal of Immunology DOI: 10.1111/sji.12895 Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an emerging coronavirus that belongs to the β genus, causing the outbreak of coronavirus disease 19 (COVID‐19). SARS‐CoV‐2 infection can stimulate a pronounced immune response in the host, which embodies in the decrease of lymphocytes and aberrant increase of cytokines in COVID‐19 patients. SARS‐CoV‐2 RNA and proteins interact with various pattern recognition receptors that switch on antiviral immune responses to regulate viral replication and spreading within the host in vivo . However, overactive and impaired immune responses also cause immune damage and subsequent tissue inflammation. This article focuses on the dual roles of immune system during SARS‐CoV‐2 infection, providing a theoretical basic for identifying therapeutic targets in a situation with an unfavorable immune reaction. The trinity of COVID-19: immunity, inflammation and intervention Authors: Tay MZ et al Publication date: 28 April 2020 Journal: Nature Reviews Immunology DOI: 10.1038/s41577-020-0311-8 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation. |
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Media – Science related |
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Vaccines |
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Oxford COVID-19 vaccine to begin phase II/III human trials Publication date: 22 May 2020 Source: University of Oxford Our vaccine work is progressing quickly. To ensure you have the latest information or to find out more about the trial, please check our latest COVID-19 vaccine news or visit the COVID-19 trial website. The phase I trial in healthy adult volunteers began in April. More than 1,000 immunisations have been completed and follow-up is currently ongoing. The next study will enrol up to 10,260 adults and children and will involve a number of partner institutions across the country. Publication date: 21 May 2020 Source: AstraZeneca Company working on a number of agreements in parallel to ensure broad and equitable supply of the vaccine throughout the world at no profit during the pandemic First agreements to supply at least 400 million doses; Company has total capacity sourced for one billion doses through 2020 and into 2021; continues to increase capacity further More than $1bn US BARDA investment to support development and production of the vaccine. £131m investment fast-tracks UK coronavirus vaccine production Publication date: 17 May 2020 Source: UK Research and Innovation (UKRI) The UK will have state-of-the-art vaccine manufacturing facilities, able to make up to 40 million doses of coronavirus vaccine by the end of the year, thanks to a UK Research and Innovation (UKRI) investment of £131 million. The funding will speed construction and grow the capacity of the Vaccines Manufacturing and Innovation Centre (VMIC), a state-of-the-art vaccine production facility that’s being built in Oxfordshire. And it will support the creation of a “virtual VMIC” in which the manufacturing facilities are temporarily created in other premises before the giant building in Oxfordshire is ready. “Virtual VMIC” will be able to produce up to 40 million doses of covid-19 vaccine within months of a successful vaccine being approved for production. |
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Therapeutics |
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Montreal researchers propose a treatment for COVID-19 Authors: Abbas Mehrabian and Sepideh Mikaeeli Publication date: 17 March 2020 Source: The McGill Tribune The World Health Organization declared COVID-19 a global pandemic on March 11. As of press time, the coronavirus had rapidly spread to more than 175,000 people in 162 countries and caused nearly 7,000 deaths. Doctors Michel Chrétien and Majambu Mbikay, senior researchers at the Montreal Clinical Research Institute (IRCM), have proposed the use of a plant-based compound called quercetin to treat COVID-19. Clinical trials to test its effectiveness are scheduled to start in China within the next few weeks. Chrétien and Mbikay say that quercetin, which some research suggests can protect against the Ebola and Zika viruses, may be able to treat the coronavirus. Working with Chinese health officials, they will supervise clinical trials for testing the drug on patients in China. They will use the drug produced by the Swiss company Quercegen Pharmaceuticals, which, according to Chrétien, produces the purest available quercetin. The trials will last around four months. |
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Schools reopening |
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June 1 too early to re-open schools: Independent SAGE Publication date: 22 May 2020 Source: Independent SAGE Committee Schools should not re-open on June 1, Independent SAGE reports today, because there is ‘no clear evidence’ that it is safe to do so. The committee of independent scientists chaired by Sir David King, the former Chief Scientific Advisor, has released a ‘draft consultation report’ which says that schools should not re-open until local ‘test, track, and isolate’ systems are in place. ‘There is no clear evidence that these conditions are met. Until they are it is not safe to open schools on June 1,’ the report says. New modelling shows delaying school re-opening by two week approximately halves the risk to children, and that delaying the re-opening until September is less risky still – reducing the risk to children to below road traffic accident level. The report notes that further modelling is needed to show regional risks and that it intends to do so before issuing its final recommendations to the government next week. The Independent SAGE’s interim report on schools Should Schools Reopen? This report is the Independent SAGE’s interim findings and concerns – a draft document for public discussion. Please read the report here. UK Cabinet Office Minister Michael Gove has re-asserted the Government’s position that state schools should reopen from 1 June if certain conditions are met. But this has provoked a mixed response with considerable questions being raised by parents, headteachers, teaching unions, local authorities and health professionals. Many Local Authorities have come forward saying they are not ready, and the British Medical Association and teachers’ unions are urging caution. While there is no dispute that schools play a fundamental role in the development of children’s emotional, social and intellectual development, it is also important to remember that schools are embedded within communities. The issue of schools reopening during COVID-19 does not just have implications for pupils; it also has knock-on effects for adult staff, parents and the communities and locality from which pupils come from. That said we recognise the issues facing decision-makers are complex, with the task of balancing numerous, different and sometimes conflicting needs of children, parents, and teaching and school support staff. We understand that there is an imperative for children to return to school for their own wellbeing, and that this will also enable some parents to return to work (others will clearly have to remain at home if there is no provision for the children to go to school), but it is also vital that an appropriate level of safety for children, staff and the wider community is ensured. |
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Media – Reporting |
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Testing |
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Tens of thousands of coronavirus tests have been double-counted, officials admit Authors: Mason Boycott-Owen and Paul Nuki Publication date: 21 May 2020 Source: The Telegraph Tens of thousands of Covid-19 tests have been double-counted in the Government’s official tally, public health officials have admitted. Diagnostic tests which involve taking saliva and nasal samples from the same patient are being counted as two tests, not one. The Department of Health and Social Care and Public Health England each confirmed the double-counting. This inflates the daily reported diagnostic test numbers by over 20 per cent, with that proportion being much higher earlier on in the crisis before home test kits were added to the daily totals. |
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Vaccines |
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Xi seeks victory over Trump in race for a COVID-19 vaccine Publication date: 26 May 2020 Source: BNN Bloomberg President Xi Jinping’s government is throwing the might of the Chinese state behind the country’s vaccine developers as the world races to make a shot against the coronavirus. The sheer scale and speed of China’s effort ratchets up pressure on the U.S., where President Donald Trump’s administration has launched a program called Operation Warp Speed to accelerate vaccine research and development. Xi has promised to share any successful vaccine globally, and the Chinese president would wield immense geopolitical clout if his country produces one of the world’s first working shots. In total, five vaccines developed by Chinese companies are being tested on humans, the most in any country. Beijing has mobilized its health authorities, drug regulators and research institutes to work around the clock with local companies. Why we might not get a coronavirus vaccine Author: Ian Sample Publication date: 22 May 2020 Source: The Guardian It would be hard to overstate the importance of developing a vaccine to Sars-CoV-2 – it’s seen as the fast track to a return to normal life. That’s why the health secretary, Matt Hancock, said the UK was “throwing everything at it”. But while trials have been launched and manufacturing deals already signed – Oxford University is now recruiting 10,000 volunteers for the next phase of its research – ministers and their advisers have become noticeably more cautious in recent days. This is why. The world needs Covid-19 vaccines. It may also be overestimating their power Author: Helens Branswell Publication date: 22 May 2020 Source: STAT With a little luck and a lot of science, the world might in the not-too-distant future get vaccines against Covid-19. But those vaccines won’t necessarily prevent all or even most infections. In the public imagination, vaccines are often seen effectively as cure-alls, like inoculations against measles. Rather than those vaccines, however, the Covid-19 vaccines in development may be more like those that protect against influenza — reducing the risk of contracting the disease, and of experiencing severe symptoms should infection occur, a number of experts told STAT. Vaccine experts say Moderna didn’t produce data critical to assessing Covid-19 vaccine Author: Helen Branswell Publication date: 19 May 2020 Source: STAT Heavy hearts soared Monday with news that Moderna’s Covid-19 vaccine candidate — the frontrunner in the American market — seemed to be generating an immune response in Phase 1 trial subjects. The company’s stock valuation also surged, hitting $29 billion, an astonishing feat for a company that currently sells zero products. But was there good reason for so much enthusiasm? Several vaccine experts asked by STAT concluded that, based on the information made available by the Cambridge, Mass.-based company, there’s really no way to know how impressive — or not — the vaccine may be. While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data. That’s important: If you ask scientists to read a journal article, they will scour data tables, not corporate statements. With science, numbers speak much louder than words. Get Ready for a Vaccine Information War Author: Kevin Roose Publication date: 13 May 2020 Source: The New York Times The other night, midway through watching a clip from “Plandemic” — a documentary that went viral on social media last week, spreading baseless lies and debunked nonsense about the coronavirus to millions of Americans overnight — I had a terrifying thought: What if we get a Covid-19 vaccine and half the country refuses to take it? It occurred to me that all the misinformation we’ve seen so far — the false rumors that 5G cellphone towers fuel the coronavirus, that drinking bleach or injecting UV rays can cure it, that Dr. Anthony Fauci is part of an anti-Trump conspiracy — may be just the warm-up act for a much bigger information war when an effective vaccine becomes available to the public. This war could pit public health officials and politicians against an anti-vaccination movement that floods social media with misinformation, conspiracy theories and propaganda aimed at convincing people that the vaccine is a menace rather than a lifesaving, economy-rescuing miracle. |
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Health passports |
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Coronavirus digital health passport to be supplied to 15 countries Publication date: 11 May 2020 Source: Verdict Manchester-based cybersecurity firm VST Enterprises has signed a deal with digital health company Circle Pass Enterprises (CPE) to create a digital health passport designed to make it easier for individuals to return to work after the Covid-19 coronavirus pandemic. The two companies have partnered to create “the world’s most secure digital health passport”, known as Covi-pass, and will work with governments and the private sector to deploy the technology to 15 countries around the world. These countries will include Italy, Portugal, France, Panama, India, the US, Canada, Sweden, Spain, South Africa, Mexico, United Arab Emirates and The Netherlands, with the goal of supplying 50 million digital health passports. The first passports will begin shipping from next week. VST Enterprises’s VCode and VPlatform technologies will be integrated into the into the Covi-pass to ensure it is secure. |
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Social Impacts |
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California Doctors Say Suicide Deaths Exceed Coronavirus Fatalities Author: Bill Sardi Publication date: 23 May 2020 Source: Lew Rockwell A California doctor says he has seen a year’s worth of suicides in the last four weeks of lockdown. More people reportedly died of suicide in one Tennessee county than from coronavirus across the whole state. A spokesperson for the Well Being Trust in Oakland, CA issued a report that predicts up to 75,000 deaths from drug or alcohol abuse and suicide directly caused by lockdowns due to the coronavirus. Fear, dread and isolation are the words used to describe these deaths of despair. Fear of unemployment, no future, forced vaccination, have caused many to give up hope. This report emanates from California where the governor just prolonged the forced lockdown another 90 days. Another study conducted by Just Facts predicts lockdowns will destroy 7 times more years of human life than strict lockdowns can save. 600 Physicians Say Lockdowns Are A ‘Mass Casualty Incident’ Author: Grace-Marie Turner Publication date: 22 May 2020 Source: Forbes More than 600 of the nation’s physicians sent a letter to President Trump this week calling the coronavirus shutdowns a “mass casualty incident” with “exponentially growing negative health consequences” to millions of non COVID patients. “The downstream health effects...are being massively under-estimated and under-reported. This is an order of magnitude error," according to the letter initiated by Simone Gold, M.D., an emergency medicine specialist in Los Angeles. “Suicide hotline phone calls have increased 600%,” the letter said. Other silent casualties: “150,000 Americans per month who would have had new cancer detected through routine screening.” |
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